CMV is associated with widespread morbidity and mortality. Infection with cytomegalovirus (CMV) is common, and it has been estimated that between 50% and 85% of people in the United States have had a CMV infection by the time they are 40 years old. Although CMV infection generally does not produce symptoms in healthy adults, high-risk groups, including immunocompromised organ transplant recipients and HIV-infected individuals, are at risk of developing CMV-associated disease. In addition, CMV is an important cause of congenital infection in the developed world, leading to mental retardation and developmental disabilities.
CMV is a member of the herpesvirus family in any species. In human, CMV, also referred to as HCMV, is designated as human herpesvirus 5 (HHV-5). CMV is the largest member of the herpesvirus family, with a double-stranded DNA genome of more than 240 kbp, capable of encoding more than 200 potential protein products. CMV is also referred to as a Betaherpesvirinae, since it is a herpes virus that infects mononuclear cells and lymphocytes. Humans are the only natural host for CMV infection, although other mammals are infected with other forms of CMV.
Medical care for patients suffering from CMV-associated disease consists of nutritional support, supportive care for end-organ syndromes (particularly pneumonia in immunocompromised patients), and specific antiviral therapy. At least three antiviral therapies are approved by the US Food and Drug Administration (FDA) for treatment or prevention of CMV infection. These include the nucleosides: ganciclovir (GCV) and cidofovir, as well as foscarnet. GCV is commonly used as preemptive therapy in transplant recipients at high risk of developing disease. Acyclovir has also been used as prophylaxis for solid organ transplantation, but the bioavailability is poor, and no data support use in children. Immunoglobulins have also been used as passive immunization for the prevention of CMV-associated disease. In general, while these agents have shown efficacy in treating or preventing CMV infection, nucleosides, in particular, are associated with serious side effects, including anemia and other blood problems. Accordingly, their use in children is limited.
Clearly, there is a need in the art for new agents useful for the treatment and prevention of symptomatic CMV infection and associated diseases, particularly for the treatment of children.